Scientists Discover New Clues About How Running May Guard Against Cancer

Mice that ran on a wheel developed fewer tumors by a large margin.

If you had only 20 or 25 minutes to make yourself feel a bit less like a sack of wet flour, running is the only way to go. I say this anecdotally, but there's a Library of Babel's worth of "running is good, really good" data to back me up. It's great for mental health, cognitive functioning, aging, and just generally like every single one of your physiological systems. Running is A+ #1 forever.

Running is also great for holding off cancer. We know well enough that regular physical exercise can limit the development and recurrence of cancer, and there has been evidence that it can improve outcomes and functional capacity in cancer patients even to the point of suppressing tumors, but the mechanisms behind this have been murky. This is where a new study in the journal Cell comes in, describing not just the tumor-limiting effects of voluntary running in mice, but also how that limiting actually happens via the activation of immune cells known as NK or "natural killer" cells, a type of lymphocyte or white blood cell whose function is all in the name.

"The immune system has a powerful capacity to combat cancer, but chronic inflammation has also been linked to tumorigenesis in several conditions," the study, which is authored by a team of oncologists led by Copenhagen University Hospital's Pernille Hojman, explains. "On the protective side, infiltrating cytotoxic immune cells have been demonstrated as positive prognostic factors for disease outcome and overall survival in several cancers. Thus, mobilization of cytotoxic immune cells during exercise might represent an indirect defense mechanism against cancer growth."

In addition to encouraging the production of "natural killer" immune cells, running also made for better tumor microenvironments for those cells to be effective

It turns out that mice are naturally pretty into running, probably way more than you are. The cancer-afflicted mice in Hojman's experiments would jump on the wheel for an average of between 4 and 7 kilometers per day, depending on the group. The first aspect of the study was measuring tumor development in mice that ran vs. those that didn't. (Not every mouse is as enthusiastic about running, it seems.) The group found an average 60 percent decrease in tumor growth and incidence among the runners compared to the non-runners.

Meanwhile, running mice injected with an agent known to cause liver cancer had an incidence of tumor development of 31 percent in the runners compared to 75 percent of the non-runners. In female mice with lung cancer, running decreased tumor volume by 58 percent and tumor weight by 56 percent. Impressive, but not all that surprising.

The real revelation in Hojman and co's paper seems to be in how the mice accomplished this physically. "Tumors from running mice showed markedly increased infiltration of NK cells, as well as CD3 T cells and dendritic cells," the group reports. It all comes back to triggering the immune system. An increase in NK cells was also seen in non-tumor bearing mice within bone marrow and blood cells.

"In tumor-bearing mice, running did not alter the frequency of NK cells in these organs, yet these mice showed pronounced accumulation of NK cells in their tumor," the study continues.

In addition to encouraging the production of NK cells, running also made for better tumor microenvironments for those cells to be effective. This "NK cell activating milieu" featured compounds that helped the NK cells target the tumors and compounds that stimulated the NK cells—which is bad for cancer.

Most all of this traces back to increases in the hormone epinephrine (or adrenaline) paired with increases in the inflammation-regulating signaling molecule IL-6. The relationship is complex, however. "In further support of the beneficial role of IL-6 exclusively in the exercise setting, we found no protective beneficial effect of IL-6 injection alone on tumor growth or intratumoral NK cell infiltration, stressing the dependence on prior training-dependent mobilization of NK cells," the study notes. No shortcuts, in other words.